Many of the effects of acute alcohol exposure and long-term abuse are correlated with changes in hippocampal function, or can be mimicked by experimental manipulations of the hippocampus. Hippocampal cholinoceptive neurons and their cholinergic afferents appear to be particularly responsive to ethanol. Recent studies also indicate important gender-related differences in the morphology and function of hippocampal neurons and in cholinergic neurotransmission which may be relevant to an understanding of differences in the effects of ethanol in males and females. Little research is available, however, evaluating gender differences or effects of hormonal influences in hippocampal neuronal responses to acute and chronic ethanol. This may be particularly important to permit an understanding of ethanol effects in special populations under conditions of altered hormonal states, for example post-menopausal women with and without hormone replacement therapy. Since previous research from this laboratory has suggested an important involvement of hippocampal neurons in the central effects of ethanol, and significant gender differences and hormonal influences may exist in hippocampal neuronal function, it is important to determine the contribution of gender and hormonal status to individual differences in ethanol responses. The project proposed here is an exploratory/developmental study to obtain initial information about the relevance of gender in the determination of acute and chronic ethanol effects on hippocampal function and possible modulation of these effects by endogenous or exogenously-applied hormones. The research proposed here will characterize the neuronal activity of pyramidal cells within the hippocampal CA1 and CA3 regions in male and female animals, and will determine the response of cells in these areas to the local application of the neurotransmitters acetylcholine, glutamate, and GABA. The proposed studies will determine the effects of acute, intrahippocampal ethanol application upon the activity of hippocampal pyramidal cells in male and female laboratory rats, and will investigate the effects of chronic ethanol exposure and withdrawal on the activity of those cells. Gender differences will be determined by comparing effects observed in normal and castrated males to those observed in normal females at different stages in the estrous cycle and in ovariectomized animals, with and without hormone replacement. This research will obtain important information regarding gender differences and hormonal influences on hippocampal function and interactions with ethanol effects. The information obtained may be of importance in understanding and developing treatments for the effects of acute and chronic ethanol on behavior, cognitive functioning, and neuronal morphology.